Regina Maria Pereira

The renin–angiotensin system and diabetes: An update

In the past few years the classical concept of the renin–angiotensin system (RAS) has experienced substantial conceptual changes. The identification of the renin/prorenin receptor, the angiotensin converting enzyme homologue ACE2 as an angiotensin peptide processing enzyme, Mas as a receptor for Ang-(1–7) and the possibility of signaling through ACE, have contributed to switch our understanding of the RAS from the classical limited proteolysis linear cascade to a cascade with multiple mediators, multiple receptors, and multi functional enzymes. In this review we will focus on the recent findings related to RAS and, in particular, on its role in diabetes by discussing possible interactions between RAS mediators, endothelium function, and insulin signaling transduction pathways as well as the putative role of ACE2-Ang-(1–7)-Mas axis in disease pathogenesis.

Current knowledge on esophageal atresia

Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is the most common congenital anomaly of the esophagus. The improvement of survival observed over the previous two decades is multifactorial and largely attributable to advances in neonatal intensive care, neonatal anesthesia, ventilatory and nutritional support, antibiotics, early surgical intervention, surgical materials and techniques. Indeed, mortality is currently limited to those cases with coexisting severe life-threatening anomalies. The diagnosis of EA is most commonly made during the first 24 h of life but may occur either antenatally or may be delayed. The primary surgical correction for EA and TEF is the best option in the absence of severe malformations. There is no ideal replacement for the esophagus and the optimal surgical treatment for patients with long-gap EA is still controversial. The primary complications during the postoperative period are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal dysmotility, fistula recurrence, respiratory disorders and deformities of the thoracic wall. Data regarding long-term outcomes and follow-ups are limited for patients following EA/TEF repair. The determination of the risk factors for the complicated evolution following EA/TEF repair may positively impact long-term prognoses. Much remains to be studied regarding this condition. This manuscript provides a literature review of the current knowledge regarding EA.

Circulating renin Angiotensin system in childhood chronic renal failure: marked increase of Angiotensin-(1-7) in end-stage renal disease.

The aim of the present study was to evaluate plasma renin activity (PRA) and Angiotensin (Ang) levels [Ang I, Ang II and Ang-(1–7)] to examine the circulating Renin-Angiotensin System (RAS) in renal disease among children with different forms and stages of chronic renal failure (CRF). Subjects were divided as follows: 32 normotensive healthy subjects, 23 normotensive CRF subjects, 34 hypertensive CRF subjects and 21 subjects with end-stage renal disease (ESRD). Radioimmunoassays for PRA (ngAngI/mL/h) and angiotensin (pg/mL) measurements were performed on all subjects. PRA, Ang I, Ang II and Ang-(1–7) levels were significantly higher in hypertensive CRF subjects when compared with normotensive CRF and healthy subjects (p < 0.05 for all comparisons). No differences were observed between normotensive CRF and healthy subjects. ESRD subjects exhibited a dramatic increase in Ang-(1–7) (25-fold higher than control values). In hypertensive CRF subjects, treatment with angiotensin-converting enzyme inhibitors (ACEi) increased (1.4-fold) plasma Ang-(1–7) and decreased (2.4-fold) Ang II. In ESRD, the use of ACEi produced a similar (1.5-fold) elevation of Ang-(1–7), but no changes in plasma Ang II. Our data showed different circulating RAS profiles between hypertensive and in normotensive CRF subjects. Marked changes in plasma Ang-(1–7) were associated with the presence of hypertension and progression of kidney dysfunction.

The Therapeutic Potential of Angiotensin-(1-7) as a Novel Renin- Angiotensin System Mediator

In this review, we show Angiotensin-(1-7) as a novel Renin Angiotensin System mediator that antagonizes cardiovascular and proliferative effects of Angiotensin II and exerts complex renal actions. We also speculate the possibility of new drugs for the treatment of cardiovascular, genitourinary and hepatic diseases by interfering with ACE2-Angiotensin-(1-7)-Mas axis.

Primary versus secondary hypertension in children followed up at an outpatient tertiary unit

Childhood hypertension has classically been recognized as a secondary disease. However, primary hypertension also occurs in children. The aim of this study was to compare clinical features of pediatric patients with elevated blood pressure, which were referred to an outpatient tertiary unit, and to detect variables associated with the identification of primary hypertension. The records of 220 patients with hypertension followed between 1996 and 2006 were analyzed. The variable of interest was primary hypertension. Logistic regression analysis was applied to identify clinical variables that were independently associated with primary hypertension. Of 220 patients, 33 (15%) had primary hypertension, and 187 (85%) exhibited secondary hypertension. No statistically significant differences were detected in gender, race, age at diagnosis, and systolic/diastolic blood pressure levels between both groups. After adjustment, four variables at baseline remained independently associated with primary hypertension: absence of signs/symptoms (OR 18.87, 95% CI 6.32–56.29), normal serum creatinine (OR 0.02, 95% CI 0.00–0.27), family history of hypertension (OR 3.03, 95% CI 1.04–8.79), and elevated body weight (OR 1.06, 95% CI 1.02–1.10). The absence of signs/symptoms, normal serum creatinine, family history of hypertension, and overweight/obesity at admission are clues to diagnose primary hypertension in childhood.

Urinary cytokine profiles according to the site of blockade of therenin-angiotensin system in nephrectomized rats

INTRODUCTION It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. OBJECTIVE This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). METHODS Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg); ¾ Nephrectomy receiving candesartan (10 mg/kg) and ¾ Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake, mean arterial pressure (MAP) and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL) -1β, IL-6, IL-10 and transforming growth factor beta (TGF-β) were measured. RESULTS Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1β, while only candesartan reduced TGF-β and only aliskiren increased IL-10. CONCLUSION Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade.